Transcript: Theresa Cerulli, MD: Ann, I know you're also involved in many studies on pipeline medications, pipeline products. Are there any other agents that you have your eyes on?
Ann C. Childress, MD: There are a number. Probably the closest to being approved by the FDA is serdexmethylphenidate. There are actually 2 different formulations. One is KP484, which is actually a prodrug of dexmethylphenidate. It was developed with the idea to have significantly lower abuse-related effects than dexmethylphenidate extended-release, or Focalin XR.
There was an intranasal administration study and an oral study. They looked at those effects with Focalin XR and also phentermine, and the abuse liability; the liking was lower. We'll see how that pans out.
Another formulation of serdexmethylphenidate includes about 30% of immediate-release dexmethylphenidate. This was looked at in an analog classroom study. Kids were dose optimized with the medication and then they came into a classroom environment, took math tests, played academic games. We looked at onset and duration of effect. With a number of different measures, onset was within about 30 minutes and duration of effect was all the way out to 13 hours. So we'll see how that pans out. That drug was actually submitted as a new drug application to the FDA last month. So it will probably be right behind viloxazine, as far as approval.
There are other stimulants that are further behind. Cingulate Therapeutics, LLC has 2 compounds, CTx-1301 and CTx-1302. CTx-1301 is an extended-release dexmethylphenidate. It was developed to have a fast onset. They're hoping the onset will be within 30 minutes and with a duration of up to 16 hours. It's very early in development. They just did the bioequivalence studies. Those were just completed and the data haven't been released yet. It also has an amphetamine sister, CTx-1302, with similar intentions—fast onset, extended duration—but that’s even further behind in development.
There are also some stimulants that are abuse-deterrent formulations. We have KP484, and then also 2 other ones. Probably the furthest along is AR19. It is a racemic D- and L-amphetamine. So it's bioequivalent to Evekeo. There are pellets in these capsules that deter manipulation for IV [intravenous], intranasal, and smoking administration. There was also an efficacy study that was completed, but those data are not published yet. It's an immediate-release with intermediate properties.
A second abuse-deterrent amphetamine immediate-release is called Adair, and that’s being developed by Vallon Pharmaceuticals Inc. The pellets resist manipulation so it's not possible to use it intranasally or intravenously and get an effect.
Those are the stimulants, 28 options; several more are coming. And then there are some other nonstimulants that are also in development. Centanafadine is a triple reuptake inhibitor. Again, we're hearing about serotonin along with norepinephrine and dopamine. This had some early positive efficacy data, and there are very large phase 3 trials under way. And there is another drug, dasotraline, but I'm not sure what'll happen to that. It's a dopamine and norepinephrine reuptake inhibitor. It has a really long half-life—47 to 77 hours, which is a really long time for any kind of medication with ADHD [attention-deficit/hyperactivity disorder]—and it was significantly more effective than placebo in a number of different studies including some laboratory classrooms. It was submitted to the FDA, but instead of approval they got a response letter asking for more efficacy and safety data. So I'm not sure exactly where that's going to go in ADHD.
Theresa Cerulli, MD: It’s interesting to hear what the behind the scenes looks like, and the cutting-edge information. Thanks for sharing all of that, Ann.
Transcript Edited for Clarity